Caustic alkaline materials, such as NaOH, KOH and Na.sub.2 CO.sub.3 and the like, are often used as reagents in medical test kits, research laboratories and industrial processes and as cleaning agents (e.g. drain cleaners, washing powders, soaps). Because of the wide usage and availability of such materials, toxic exposures occur with reasonable frequency. Accidental exposure from the ingestion of caustic alkali is a particularly serious problem among children. In the United States at least 5000 serious ingestions of caustic alkali occur each year among children. The consequences from ingestion may occur acutely with esophageal wall necrosis leading to esophageal perforation and death; subacutely to esophageal obstruction from stricture formation; or chronically to an increased risk of developing esophageal squamous cell carcinoma. See L. Leape et al., N. Engl. J. Med. 284, 578-81 (1971); P. Loeb and A. Eisenstein, in: Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 148-155 (M. Sleisenger and J. Fordtran Eds. 1983)(WB Saunders Company, Philadelphia, Pa.). Chemical burns resulting from caustic alkali splashing onto skin and into the eye are also serious problems associated with accidental exposure. The former potentially leads to disfigurement and the latter to blindness from corneal ulceration (Advanced Trauma Life Support Course, American College of Surgeons Committee on Trauma; 1989; page 208).
The damage caused by the exposure of body tissues to caustic alkali is due to the high pH of such substances. Treatments of alkali exposure, therefore, focus on the reduction of pH towards normal (pH 7.4) as quickly as possible. With external surfaces of the body, e.g. skin and eye, washing with water (known as hydrotherapy in the case of corneal burns) is the major method used to reduce tissue pH. In such cases, the water dilutes and removes the alkaline material. There is data, however, indicating that even after a single exposure of alkali to skin, a stratified squamous epithelial-lined organ, the alkalinity of the tissue remains high for many hours (&gt;12 hours). See R. Gruber et al., Plast. Reconstr. Surg. 55, 200 (1975). Such prolonged tissue alkalinity is reportedly due to the propensity of alkali to form soluble protein-hydroxyl ion complexes that serve to further permit the penetration of alkali into the underlying tissue. M. Kirsh and F. Ritter, Ann. Thorac. Surg. 21, 74-82 (1976). For this reason, continued washing (or hydrotherapy in the case of corneal burns) for many hours has been recommended to reduce the degree of alkaline injury.
For caustic alkali ingestions, the major risk of damage is to the stratified squamous epithelial-linings of the oral cavity and esophagus. The recommended treatment for oral contact of a caustic alkali, for example lye, is washing with water. In contrast, there is no general agreement on the treatment of lye exposure to esophagus. Some suggest the immediate ingestion of weakly acidic substances, e.g. vinegar, to neutralize the alkali. Others suggest this not be done because of the concern that dilution and neutralization of alkali by weak acids may yield enough heat from an exothermic reaction to increase, not decrease, the degree of tissue injury and that in severe burns of the esophageal wall such attempts will cause the patient to gag, wretch, vomit and in so doing aspirate or convert the burned and weakened esophageal wall into a perforation risking death acutely from mediastinitis. P. Loeb and A. Eisenstein AM, supra. B. Rumack and J. Burrington, Clin. Toxicol. 11, 27-34 (1977). Therefore, at present the majority view recommends "nothing by mouth" as therapy for lye ingestion.
The majority of serious lye ingestions do not lead to esophageal perforations and death. Thus the most serious concern, and most common complication, is the development of an esophageal stricture. Esophageal stricture results from transepithelial necrosis and healing by scar (fibrosis) formation. For this reason current therapeutic approaches focus less on trying to reduce the degree of acute injury than on trying to prevent stricture formation, even though it is recognized that the major determinant of stricture formation is the depth and extent of the acute injury. To date, however, no agent has proven beneficial. Even the administration of corticosteriods was recently documented to be of no benefit in reducing stricture formation. See K. Anderson et al., New Engl. J. Med. 323, 637-640 (1990).
From the foregoing it is evident that a rapid, safe and effective means of reducing tissue alkalinity after exposure of skin, eye, mouth, oral cavity, esophagus, and other tissues, to caustic alkaline substances is sorely needed to reduce the morbidity (and in some cases mortality) from this disorder.